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Heparin products are widely used clinical anticoagulants essential in the practice of modern medicine. Low-molecular-weight heparins (LMWHs) are currently prepared by the controlled chemical or enzymatic depolymerization of unfractionated heparins (UFHs) that are extracted from animal tissues. In many clinical applications, LMWHs have displaced UFHs and currently comprise over 60% of the heparin market. In the past, our laboratory has made extensive efforts to prepare bioengineered UFHs relying on a chemoenzymatic process to address concerns about animal-sourced UFHs. The current study describes the use of a novel chemoenzymatic process to prepare a chemobiosynthetic LMWH from a low-molecular-weight heparosan. The resulting chemobiocatalytic LMWH matches most of the United States pharmacopeial specifications for enoxaparin, a LMWH prepared through the base-catalyzed depolymerization of animal-derived UFH.


Yanlei Yu, Li Fu, Peng He, Ke Xia, Sony Varghese, Hong Wang, Fuming Zhang, Jonathan Dordick, Robert J Linhardt. Chemobiocatalytic Synthesis of a Low-Molecular-Weight Heparin. ACS chemical biology. 2022 Mar 18;17(3):637-646

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PMID: 35201757

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